An Independent Data Monitoring Committee (IDMC) unanimously recommended that the Phase III Resonate? trial,a head-to-head comparison ofIbrutinib (PCI-32765,Imbruvica?;Pharmacyclics)versus ofatumumab, be stopped early because the primary and a key secondary endpoint of the study have been met.

Resonateis a randomized, multicenter, open-label Phase III study of single agent ibrutinib versus single agent ofatumumab in patients with relapsed or refractory CLL or relapsed or refractory SLL with measurable nodal disease and who were not eligible for treatment with purine analog-based therapy. The study enrolled 391 patients who had received at least one prior therapy. Patients were randomized to receive 420 mg of Ibrutiniborally once daily or intravenous doses of ofatumumab over the course of 24 weeks until disease progression or unacceptable toxicity. Patients randomized to the ofatumumab arm who experienced disease progression were evaluable for consideration of subsequent Ibrutinibtherapy.

Slow-growing
CLL, a B-cell malignancy, is a slow-growing blood cancer of the white blood cells (lymphocytes), most commonly from B-cells. CLL is the second most common adult leukemia. Approximately 16,000 patients in the U.S. are diagnosed each year with CLL.

The prevalence of CLL is approximately 113,000 in the U.S. CLL is a chronic disease that predominantly occurs in the elderly with a five-year survival of approximately 82 percent. Patients commonly receive multiple lines of treatment over the course of their disease.

When cancer cells are located mostly in the lymph nodes, the disease is called SLL. CLL and SLL are considered to be different manifestations of the same underlying disease; they share similarities in signs and symptoms, genetic features, disease progression and treatment.

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Statistically significant improvement
At the planned interim analysis, the Phase III Resonatestudy demonstrated that Ibrutinibshowed a statistically significant improvement in progression-free survival, the primary endpoint of the study, which was evaluated by an independent review committee, in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).


…The vigilance and professional expertise that our IDMC exercised in monitoring this study resulted in a robust and consistent interim analysis…


Further, Ibrutinibshowed statistically significant improvement in overall survival, a key secondary endpoint of the trial. The safety profile of Ibrutinibwas acceptable and consistent with prior clinical experience. The IDMC recommended that the sponsor provide access to Ibrutinibfor subjects on the ofatumumab arm.

“The vigilance and professional expertise that our IDMC exercised in monitoring this study resulted in a robust and consistent interim analysis,” said Fong Clow, Sc. D, Senior Vice President of Biometrics at Pharmacyclics.

Health authorities
Pharmacyclics has informed the U.S. Food and Drug Administration (FDA) of the recommendations of the IDMC. Similarily, Janssen, the co-developer of Ibrutinib, has informed the European Medicines Agency (EMA). Both companies are engaging in a dialogue with the Health Authorities to define the next regulatory steps and anticipate providing a comprehensive Resonatestudy report to them within the coming months.

“This collaboration resulted in expeditious enrollment, and rapid data collection and analysis. This global study involving 391 patients was conducted at more than 70 clinical sites in 10 countries,” said Maria Fardis, PhD, Chief of Oncology Operations and Alliances at Pharmacyclics.

“We express our appreciation to the patients, the investigators and the entire Pharmacyclics and Janssen teams for overcoming the barriers and challenges associated with this exciting scientific outcome,” explained Robert Duggan, Chief Executive Officer and Chairman of the Board of Pharmacyclics.

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